Myocardial commitment from human pluripotent stem cells: Rapid production of human heart grafts

Biomaterials. 2016 Aug;98:64-78. doi: 10.1016/j.biomaterials.2016.04.003. Epub 2016 Apr 26.


Genome editing on human pluripotent stem cells (hPSCs) together with the development of protocols for organ decellularization opens the door to the generation of autologous bioartificial hearts. Here we sought to generate for the first time a fluorescent reporter human embryonic stem cell (hESC) line by means of Transcription activator-like effector nucleases (TALENs) to efficiently produce cardiomyocyte-like cells (CLCs) from hPSCs and repopulate decellularized human heart ventricles for heart engineering. In our hands, targeting myosin heavy chain locus (MYH6) with mCherry fluorescent reporter by TALEN technology in hESCs did not alter major pluripotent-related features, and allowed for the definition of a robust protocol for CLCs production also from human induced pluripotent stem cells (hiPSCs) in 14 days. hPSCs-derived CLCs (hPSCs-CLCs) were next used to recellularize acellular cardiac scaffolds. Electrophysiological responses encountered when hPSCs-CLCs were cultured on ventricular decellularized extracellular matrix (vdECM) correlated with significant increases in the levels of expression of different ion channels determinant for calcium homeostasis and heart contractile function. Overall, the approach described here allows for the rapid generation of human cardiac grafts from hPSCs, in a total of 24 days, providing a suitable platform for cardiac engineering and disease modeling in the human setting.

Keywords: Cardiac function; Extracellular matrix; Gene targeting; Pluripotent stem cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cardiac Myosins / genetics
  • Cell Differentiation / drug effects
  • Cell Line
  • Collagen / pharmacology
  • Drug Combinations
  • Electrophysiological Phenomena / drug effects
  • Extracellular Matrix / metabolism
  • Genetic Loci
  • Heart Transplantation*
  • Heart Ventricles / metabolism
  • Human Embryonic Stem Cells / cytology
  • Human Embryonic Stem Cells / drug effects
  • Human Embryonic Stem Cells / metabolism
  • Humans
  • Laminin / pharmacology
  • Myocardium / cytology*
  • Myocytes, Cardiac / cytology
  • Myocytes, Cardiac / drug effects
  • Myocytes, Cardiac / metabolism
  • Myosin Heavy Chains / genetics
  • Pluripotent Stem Cells / cytology*
  • Pluripotent Stem Cells / drug effects
  • Pluripotent Stem Cells / metabolism
  • Proteoglycans / pharmacology
  • Transcription Activator-Like Effector Nucleases


  • Drug Combinations
  • Laminin
  • MYH6 protein, human
  • Proteoglycans
  • matrigel
  • Collagen
  • Transcription Activator-Like Effector Nucleases
  • Cardiac Myosins
  • Myosin Heavy Chains